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SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Acta Pharmaceutica Sinica B 2022年第8期12卷 3281-3297页

作者： Baeksun Kim Sung Hyun Tag Eunjoo Nam Suji Ham sujin ahn Juhwan Kim Doo-Wan Cho Sangjoon Lee Young-Su Yang Seung Eun Lee Yong Sik Kim Il-Joo Cho Kwang Pyo Kim Su-Cheol Han Heh-In Im Convergence Research Center for Diagnosis Treatment and Care System of Dementia(DTC)Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science&Technology KIST SchoolKorea University of Science and Technology(UST)Seoul 02792Republic of Korea Center for Neuroscience KISTSeoul 02792Republic of Korea Animal Model Research Center Jeonbuk Department of Inhalation ResearchKorea Institute of Toxicology(KIT)Korea Research Institute of Chemical Technology(KRICT)Jeongeup 56212Republic of Korea Research Animal Resource Center KISTSeoul 02792Republic of Korea Department of Pharmacology Seoul National University College of MedicineSeoul 03080Republic of Korea Center for BioMicrosystems KISTSeoul 02792Republic of Korea Department of Applied Chemistry Kyung Hee UniversityGyeonggi-do 17104Republic of Korea

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

关键词： Methamphetamine Abstinence Withdrawal Striatum miR-137 SYNCRIP Biomarker Behavior

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Super-resolution morphological dissemination of intercalating dye in single DNA molecules via binding activated localization microscopy

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Chinese Chemical Letters 2018年第3期29卷 505-508页

作者： Guenyoung Park Suresh Kumar Chakkarapani Soyeong Ju sujin ahn Seong Ho Kang Department of Chemistry Graduate School Kyung Hee University Department of Applied Chemistry and Institute of Natural Sciences Kyung Hee University

Fluorescent dye （YOYO-I） intercalated with single DNA molecules were investigated via bindingactivated localization microscopy （BALM） at sub-diffraction limit resolutions. Various dye-to-DNA base pair （bp） ratios were imaged using the blinking property of YOYO-1 dye under optimum BALM switching buffer conditions. Individual DNA molecules exhibited regular/irregular intercalating phenomena with respect to dye-to-DNA bp ratio. The acquired images were reconstructed into super-resolution images by applying a Gaussian fit to the centroid of the point spread function. The YOYO-1 intercalated with λ-DNA possessed a non-homogeneous region due to the different binding modes of YOYO-1 with λ-DNA. Each binding mode was imaged at the sub-diffraction limit super-resolution. The distance between homogenously localized intercalating dyes within the DNA molecules was measured to be 34nm （n= 10; dye：DNAbp= 1：100） without photocleavage in 50mmol/L β-mercaptoethylamine buffer. The results were similar to those of the theoretical values without photocleavage in the base pairs of single DNA molecules below the diffraction limit. The results paved the way for an in-depth microscopic analysis of molecular variation with single λ-DNA molecules. With this method, it should be possible to analyze the exact base pair breakdown during various stages of cell apoptosis.

关键词： λ-DNA Intercalating dye Morphological dissemination Sub-diffraction limit resolution Binding-activated localization microscopy

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